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PI-103
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
PI-103图片
CAS NO:371935-74-9
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议
1g电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)348.36
FormulaC19H16N4O3
CAS No.371935-74-9
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 24 mg/mL (68.9 mM)
Water:<1 mg/mL (slightly soluble or insoluble)
Ethanol: <1 mg/mL (slightly soluble or insoluble)
Solubility (In vivo) 1% DMSO+30% polyethylene glycol+1% Tween 80: 30 mg/mL
Chemical Name/Synonym3-(4-morpholin-4-ylpyrido[2,3]furo[2,4-b]pyrimidin-2-yl)phenol; PI103; PI-103; PI 103
实验参考方法

In Vitro

Kinase Assay: Enzyme Assays; Phosphatidylinositide 3-kinase inhibitory activity was determined using a scintillation proximity assay in the presence of 1 μmol/L ATP. Inhibition of mTOR protein kinase was determined using a TR-FRET-based LanthaScreen method from Invitrogen. Compounds were assayed at a maximum concentration of 10 μmol/L in the presence of 1 μmol/L ATP, and IC50 values were determined using GraphPad Prism software.

Cell Assay: U87MG cells are treated with PI-103 for 24 hours. Cell death is quantified by colorimetric determination of LDH activity using a cytotoxicity detection kit. Percentage of cell death (mean of three 12-well plates per experimental point) is calculated [(experimental value- low control)/(high control -low control) × 100], where the low-control cells are DMSO treated and high-control cells are Triton treated (1% Triton X-100, 30 min, 37 °; Concentration: 0.5 μM

PI-103 potently inhibits both the rapamycin-sensitive (mTORC1) and rapamycin-insensitive (mTORC2) complexes of the protein kinase mTOR. PI-103 inhibits constitutive and growth factor-induced PI3K/Akt, as well as mTORC1 activation. In blast cells, PI-103 inhibits leukemic proliferation, the clonogenicity of leukemic progenitors and induces mitochondrial apoptosis, especially in the compartment containing leukemic stem cells. PI-103 inhibits p110α>200-fold more potently than p110β. PI-103 also potently blocks production of PI(3,4)P2 and PIP3 in adipocytes and PIP3 in myotubes. PI-103 inhibits phosphorylation of Akt with an IC95 100-fold lower than that for LY294002. Strikingly, PI-103 completely protects animals from insulin-stimulated decline in blood glucose. PI-103 has additive proapoptotic effects with etoposide in blast cells and in immature leukemic cells.

In Vivo

When tumors reach 50-100 mm3, animals are randomized and treated with vehicle or PI-103. PI-103 exhibits significant activity, decreasing average tumor size by 4-fold after 18 days. Mice treated with PI-103 have no obvious signs of toxicity premorbidly (based on body weight, food and water intake, activity, and general exam) or at necropsy. Treated tumors display decreased levels of phosphorylated Akt and S6, consistent with blockade of p110α and mTOR. PI-103 treatment is cytostatic to glioma xenografts.

Animal model

6- to 12-week-old Balbc nu/nu mice bearing U87MG:ΔEGFR cells

Formulation & Dosage

Solubilized in 50% DMSO; 5 mg/kg; i.p.

References

[1] Cell. 2006 May 19;125(4):733-47; [2] Cancer Cell. 2006 May;9(5):341-9.

生物活性





Cooperative inhibition of p110α and mTOR arrests growth of human glioma cells. Cancer Cell. 2006 May;9(5):341-9.



Inhibition of p110α and of mTOR represents a safe and effective strategy in EGFR-driven glioma in vitro and in vivo. Cancer Cell. 2006 May;9(5):341-9.